THE HAIR GROWTH CYCLE
In most mammals, hair does not grow continuously, but undergoes a cycle of activity involving periods of growth, rest and shedding. On the human scalp, from 100,000 to 350,000 hair fibers or shafts undergo metamorphosis in three distinct stages, namely:
(i) the growth phase, known as anagen, during which the hair root bulb or dermal papilla (also called the "follicular papilla") penetrates deep into the dermis with the cells of the bulb dividing rapidly and differentiating in the process of synthesizing keratin, the substance of the hair shaft itself. In normal humans, this growth phase is thought to last from one to five years; PA1 (ii) the transitional stage, catagen, is marked by the cessation of mitosis. This phase lasts from two to three weeks; and PA1 (iii) the resting stage known as telogen, where the hair is retained within the scalp for up to 12 weeks before the emerging new hair developing below it dislodges the telogen-phase shaft from its follicle. PA1 1) It has never been tested on older adults or pregnant women. PA1 2) It is not advised for people with skin problems or scalp irritation, heart disease or hypertension. For these individuals, excessive absorption of minoxidil may lead to chest pain, fast or irregular heartbeat, flushing, headaches, numbness or tingling of the hands, feet or face, swelling of feet or lower legs and rapid weight gain.
For reasons yet unknown, subjects evidencing androgenic alopecia experience gradual changes in the width and length of the hair shaft over time and with age, some prematurely. Men as early as their 20's and women in their 30's and 40's begin to notice their hair becoming finer and shorter. In addition, the ratio of growing hairs to hairs in the resting/shedding phase declines from as high as 9:1 to as low as 2:1. Exactly how and where the growth and regenerative processes is damaged has yet to be definitively understood.
It is generally accepted that genetic hair loss arises from the activation of an inherited predisposition to circulating androgenic hormones. Androgenic alopecia is the single largest type of recognizable alopecia to affect both men (50%) and women (30%), primarily of Caucasian origin. The condition is characterized by the gradual conversion of terminal hair to short, wispy, colorless vellus hair. FIGS. 1 and 2 compare a healthy terminal hair follicle to one transformed by androgenic alopecia into a vellus hair.
While many investigators have tried to isolate the causative androgen metabolite, no single molecule has emerged. Nor, in comparative studies between nonbalding controls, has a significant difference between mean hormonal values or amounts been detected. See J. Puolakka, Serum ferritin in the evaluation of iron status in young health women, Acta. Obsteto Gynecol. Scand. suppl. 95, 35-41 (1980). This suggests that a sensitivity or receptivity to hormones at the cell binding sites within the dermal papilla is a possible factor. Several treatments are based on this theory using anti-androgens such as CPA (cyproterone acetate) in combination with ethinyl-estradiol and the aldosterone antagonist spironolactone, which, given in dosages from 75 to 100 mg per day has shown some benefit. See e.g., D. H. Rushton and D. D. Ramsay, The importance of adequate serum ferritin levels in cyproterone acetate and ethinyl-oestradiol therapy in women with diffuse androgen-dependant alopecia, Clin. Endocrinol. 36, 421-427 (1992); DH Rushton, W. Futterwiet, DH Kingsley, P. Kingsley and MJ Norris, Quantitative assessment of spironolactone treatment in women with diffuse androgen-dependent alopecia, J. Soc. Cosmet. Chem. 42, 317-325 (1991).
Prior art also includes mucopolysaccharide and chondroitin sulfate in hair compositions to prevent loss and encourage growth. However, according to The Berkeley Wellness Letter, published by the University of California (June 1992, vol. 8 no. 9 pg. 4), the treatment philosophy for genetic hair loss depends predominantly upon controlling the testosterone metabolite, DHT (dihydrotestosterone). The major bio-synthetic pathway of DHT is catalyzed by the enzyme 5 alpha!-reductase. It is hypothesized by these researchers that compounds which selectively block this enzyme (by inhibiting substrate uptake or altering the binding affinity for the androgen receptor protein complex) could have a high success rate at halting premature anagen termination. In this regard, Brawn et al. (U.S. Pat. No. 5,185,325) has developed a topical application containing a glycosaminoglycanase inhibitor chosen from aldonomonolactones, alduronomonolactones and acylated monosaccharides. They identify the breakdown of glycosaminoglycans (complex polysaccharides) by male hormones as the initiating condition of the onset of catagen. This approach attempts to sustain hair growth by preventing the splitting of the glycosaminoglycan molecule at specific sites by the topical application of certain molecules such as asacylated monosaccharides. Brawn foresaw a 10% to 50% increase in hair growth versus the control. Clinical human trial data was not supplied in the patent.
As illustrated in FIG. 1, experiments with mouse hair follicles showed that the anagen phase stem cells, stored within the bulge area of the follicle, proliferated during early anagen and migrated to the root bulb region prior to differentiation. See Miller, Stanley J., Sun, Tung-Tien, and Lavker, Robert M., Hair Follicles, Stem Cells, and Skin Cancer, The Society for Investigative Dermatology, 1993. Miller et al. believe that the bulge cells can be stimulated to proliferate in response to both physical and chemical stimuli causing telogen follicles to commence anagen. In addition, the physical proximity of the follicular papilla to the bulge area containing the stem cells plays a role in the onset of anagen cycles. Miller et al. have speculated that damage to the bulge region (such as is caused by lupus erythematosus or lichen planopilaris) frequently results in permanent alopecia, whereas damage to the hair root bulb alone results in alopecia areata and is temporary.
It is noted that several of the ingredients such as salicylic acid and castor oil have been employed as hair growth stimulants. Their therapeutic functions are identified as emollients (castor oil) and irritants and keratolytics for the stimulation of blood flow (salicylic acid and spirits of camphor).
U.S. Pat. No. 5,081,151, issued to Davis, et al. relates to a method for inducing, maintaining or increasing hair growth by topically applying a preserved composition comprising an effective amount of hexosaccharic acid, salts and esters thereof.
U.S. Pat. No. 5,158,955 issued to Gibson, et al. relates to a preserved composition for topical application for inducing, maintaining or increasing hair growth which comprises a special ester of pyroglutamic acid and a cosmetically acceptable vehicle for the ester. Gibson lists salicylic acid and castor oil as hair growth stimulants. Isopropyl alcohol is also disclosed.
U.S. Pat. No. 5,185,325, issued to Brawn, et al. relates to a composition for inducing, maintaining or increasing hair growth including a glycosaminoglycanase inhibitor chosen from aldonomonolactones, alduronomonolactones and acylated monosaccharides. Brawn discloses the use of salicylic acid and castor oil as substances which stimulate or increase hair growth, and the use of penetration enhancers, such as isopropyl alcohol.
U.S. Pat. No. 4,849,214, issued to Ruiseco relates to an oil based composition for the treatment of dry scalp conditions, which includes grated avocado seed in a mineral oil solution and the addition of other ingredients, such as castor oil and spirit of camphor.
U.S. Pat. Nos. 5,130,142, issued to Wong, et al., relates to a composition for regulating hair growth which includes a supernatant derived from a culture of epithelial cells. When the composition is in lotion or cream form, it can include emollients (such as castor oil) and additionally alcohol.
U.S. Pat. No. 5,192,534, issued to Grolier, et al. relates to compositions for inducing and stimulating hair growth and/or retarding its loss containing, in combination, pyrimidine derivatives and at least some agents which screen out UV radiation.
It is also known that liquor carbonis detergens has been established as a treatment for certain skin disorders (See e.g., U.S. Pat. Nos. 4,102,995; 3,627,871; 3,472,931; 3,061,512; 3,071,510; 23,262,851; 2,622,057; and 2,602,039) and is especially effective as an antipruritic, antibacterial and keratoplastic (control of the production of epithelial keratin) in the treatment of psoriasis, often formulated as a shampoo. Nowhere, however, in the prior art of commercial or non-commercial compositions is there a reference to the use of liquor carbonis detergens as a therapy for hair loss alone or in combination with any of the ingredients identified.
A recent study conducted in Cologne, Germany Merk, H.F., Mukhtar, H., Schutte, B. et al., Department of Dermatology, University of Cologne! identified a high correlation (95%) of enzyme activation within the cells of the follicular papilla when a solution of liquor carbonis detergens was topically applied to freshly plucked roots. The researcher suggested that the cytochrome P-450 isozymes, affecting the metabolism of oxygen within the cell, was altered by this solution. It was also theorized by Levkar et al., in his study of the origin of skin cancers that most non-melanoma cancers of the skin originate in the hair follicle, suggesting that the cells of this region are more highly prone to mitosis than epithelial cells between the follicles. In fact, during the entire anagen phase the cellular activity, both in terms of migration and mitosis, is highly active, resulting in the proliferation of keratinocytes (the cells of the shaft itself).